Isothiocyanates are important as haptens in contact allergy to chloroprene rubber.

BACKGROUND: Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. OBJECTIVES: To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. METHODS: Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. RESULTS: All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm-2 . At 35 °C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. CONCLUSIONS: Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.

An oral challenge test with carmine red (E120) in skin prick test positive patients.

BACKGROUND: Positive skin prick test reactions to carmine red (E120) occur in approximately 3% of the patients studied for food allergy. Carmine ingestion associated systemic symptoms are occasionally suspected, but sufficient information of proven carmine allergy is not available. PATIENTS AND METHODS: To analyse carmine related symptoms in skin prick test positive patients a cohort of 23 patients with suspected allergy to carmine red was subjected to a single-blind placebo-controlled oral challenge test with carmine red. RESULTS: Five patients developed clinical symptoms during the placebo-controlled oral challenge. As a result, the overall frequency of clinical carmine allergy is estimated to be 0.7% in general dermatology patients studied for food-associated symptoms. CONCLUSIONS: Oral challenge test provides a valuable in vivo tool to better inform patients with positive skin prick tests to additives to avoid false allergy diets.

An epidemic of furniture-related dermatitis: searching for a cause.

Background Sitting in new chairs or sofas has elicited dermatitis in numerous patients in Finland and in the U.K. since autumn 2006. The cause of the dermatitis seemed to be an allergen in the furniture materials. Objectives To determine the cause of the dermatitis in patients with furniture-related dermatitis. Methods Altogether 42 patients with furniture-related dermatitis were studied. First, 14 Finnish patients were patch tested with the standardized series and with the chair textile material. A thin-layer chromatogram (TLC) strip and an extract made from the same textile material were tested in seven Finnish patients. The test positive spot of the TLC and the content of a sachet found inside a sofa in the U.K. were analysed by using gas chromatography-mass spectrometry. All chemicals analysed were patch tested in 37 patients. Results A positive patch test reaction to the chair textile and to its extract was seen in all patients tested, one-third of whom had concurrent reactions to acrylates. Positive reactions to the same spot of the TLC strip were seen in five of seven patients and dimethyl fumarate was analysed from the spot as well as from the sachet contents. Dimethyl fumarate (0.01%) elicited positive reactions in all the patients. The other chemicals analysed did not elicit positive reactions, but one patient in the U.K. had a positive reaction to tributyl phosphate. Conclusions Sensitization to dimethyl fumarate was seen in all the patients with furniture-related dermatitis. Concurrent sensitization or cross-reactions were common among the sensitized patients.

An outbreak of furniture related dermatitis ('sofa dermatitis') in Finland and the UK: history and clinical cases.

In February 2007, an epidemic of severe dermatitis from Chinese recliner chairs and sofas started to unfold first in Finland and a few months later in the UK. Some patients reacted in patch tests (PTs) strongly to the material of their furniture, either leather or fabric. There have been hundreds of reports of chair or sofa dermatitis from Finland and the UK, with all cases linked to the same furniture factory in China. Clinical findings in both countries were very similar and unlike any known dermatosis. Many cases have been quite severe, resembling mycosis fungoides or septic infections, requiring hospitalization. Commercial PTs did not reveal the cause but a fungicide was strongly suspected, although such use was denied by the factory. The laboratory of Malmö University Dermatology Clinic has helped in the process by making thin layer chromatograms from sofa or chair materials and test substances of suspected chemicals. Finally, sachets marked with 'mouldproof agent' were found in varying numbers and distribution in the sofas. These contained dimethyl fumarate (DMF) which proved in skin tests to cause strong positive reactions with down to 0.01 dilution. Reports from other countries (Belgium, France, Ireland, Sweden and Spain) have since appeared, and the EU has banned the use of DMF in consumer products.

Lymphocyte migration into the skin: the role of lymphocyte homing receptor (CD44) and endothelial cell antigen (HECA-452).

Lymphocyte migration into the lymphoid organs and sites of inflammation is controlled by lymphocyte-endothelial cell interaction at sites where lymphocytes exit from the blood. Expression of Hermes-defined CD44 class of lymphocyte homing receptor and HECA-452 antigen specific for high-endothelium-mediating physiologic lymphocyte extravasation was studied in dermatitis herpetiformis, celiac disease, psoriasis, mycosis fungoides, lymphocytosis cutis, atopic dermatitis, and allergic contact dermatitis. Also, duodenal biopsies of patients suffering from dermatitis herpetiformis or celiac disease were studied for existence of these antigens. Infiltrating lymphocytes in the skin and in the duodenal area expressed homing receptor molecules when studied with monoclonal antibodies, Hermes-1 and Hermes-3, that recognize the CD44 class of molecules involved in lymphocyte binding to high endothelial venules in peripheral lymph nodes, mucosa-associated lymphatic tissues, and inflamed synovium. However, the HECA-452 antigen was not detected on the venules, neither in the skin nor in the duodenum. Even the venules possessing high endothelium morphologically were HECA-452 negative. These findings suggest the CD44 class of lymphocyte homing receptor(s) is also involved in lymphocyte homing to inflamed skin and the duodenal area of the gut. However, on the basis of HECA-452 staining, high endothelial venules in inflamed skin and duodenum are not antigenically identical with high endothelial venules in organized lymphoid tissues. This finding indirectly supports the idea that molecules and/or mechanisms mediating lymphocyte extravasation might be distinct in these organs.

Presence of parvovirus B19 DNA in chronic urticaric and healthy human skin.

BACKGROUND: The etiology of chronic urticaria is undefined, but the potential role of infectious agents as one triggering factor has been suggested. The appearance of chronic urticaria in a 16-year old male after a history of a recent parvovirus B19 (B19) infection led us to investigate the association between B19 and chronic urticaria. OBJECTIVES: To investigate whether parvovirus B19 (B19) has a role in chronic urticaria. STUDY DESIGN: We amplified B19 DNA from skin biopsy samples of 36 adult chronic urticaria patients as well as of 22 healthy controls using two sets of separate primers and probe. Circulating IgG and IgM antibodies to B19 were measured from 27 patients and from all controls. RESULTS: B19 DNA was detected in 18 (50%) skin biopsy samples of 36 patients with chronic urticaria. Unexpectedly, also 14 (64%) skin biopsy samples from 22 healthy controls harbored B19 DNA. All 32 persons with positive B19 PCR findings had circulating IgG-class antibodies to B19 major structural protein VP2, but no IgM antibodies. CONCLUSION: Our results show that B19 DNA commonly exists in human skin. Therefore, the association between B19 infection and chronic urticaria remains uncertain. However, these findings raise the question whether the skin may constitute a reservoir for B19.

The usefulness of skin tests to prove drug hypersensitivity.

BACKGROUND: Suspected drug hypersensitivity is common. Only a minority of cutaneous adverse drug reactions (CADRs) are allergic in origin and will reappear after the next exposure. Methods to confirm suspected CADRs are needed and skin testing could serve as one possibility. OBJECTIVES: To analyse the usefulness of skin tests in revealing drug allergy. The relevance of skin test results was evaluated with drug provocation studies. METHODS: During 1989-2001, 947 patients with a history of suspected CADR were examined with skin tests including patch tests (PTs) (826 patients), skin prick tests (SPTs) (935 patients) and photopatch tests (12 patients). The occurrence of positive and negative test reactions to different drugs was correlated with clinical history. Drug provocation was carried out in 246 patients. RESULTS: Antimicrobial drugs were suspected and tested most often. A positive PT reaction to one or more drug was seen in 89 of 826 (10.8%), most often to beta-lactams, clindamycin and trimethoprim. A positive SPT reaction was seen in 10 of 935 (1.1%) patients. Challenge was carried out in 17 patients with positive skin test results. Thirteen of 16 (81.2%) PT positives developed exanthema, three remained negative and one SPT-positive patient developed urticaria. Among skin test negatives, 207 of 229 (90.4%) challenges were negative and 22 of 229 (9.6%) were positive, 12 with exanthema, three with fixed drug eruptions and seven with urticaria. CONCLUSIONS: Skin testing, especially the PT, was a useful screening method to find a cause of CADR if the reaction was exanthema and if antimicrobial, cardiovascular or antiepileptic drugs were suspected. The SPT detected occasional positives with antimicrobials. In cases of fixed drug eruption, PTs performed at the earlier reaction site were useful. When skin tests are negative or dubious, oral challenge should be carried out to confirm the association.

Patch test reactions to cosmetic allergens in 1995-1997 and 2000-2002 in Finland--a multicentre study.

Contact sensitivity to cosmetics is common, but the sensitizing chemicals vary between countries and study periods. The present survey aimed at revealing the recent trends in patch test sensitivity with cosmetic chemicals in Finland. We report a retrospective multicentre survey of patch test reactions focusing on cosmetic-related substances and comparing the test results in 1995-97 with those in 2000-02. The most striking increases in the frequency of the patch test sensitivity were found with balsam of Peru and propolis from 4.0% to 6.2% (P < 0.001) and from 0.5% to 1.4% (P < 0.001), respectively, whereas the most prominent decreases were found with methylchloro/methylisothiazolinone and chlorhexidine diglugonate from 2.4% to 1.3% (P < 0.001) and from 1.2% to 0.5% (P < 0.001), respectively. The level of patch test sensitivity to methyldibromo glutaronitrile increased, although not significantly, from 1.0% to 1.5%. An increasing tendency was also found with hair dye chemicals 4-aminophenol and toluene-2,5-diamine or toluene-2,5-diamine sulfate from 1.3% to 3.8% and from 1.4% to 5.2%, respectively, while such a tendency was not found among permanent wave chemicals. The sensitivity level of fragrance mix remained the same (6% - 7%). We conclude that surveys revealing the state of sensitivity to cosmetic chemicals should be performed periodically in different countries.

Does a patient's occupation influence the course of atopic dermatitis?

The importance of occupational environments in relation to the course of an atopic skin disease was investigated. A series of 1008 adult patients, who had had an atopic disease since their teenage years, were studied. Severe or moderate childhood atopic dermatitis tended to persist or relapse in adulthood independent of occupation. Only dermatitis of the hands showed a correlation with extensive daily exposure to occupational irritation factors. Atopic dermatitis patients did not go on sick leave more often than controls or those with atopic mucosal symptoms, although sick leave caused by skin problems lasted longer than sick leave caused by other circumstances. Atopic patients did not change their occupation because of their disease more often than the non-atopics. On the whole, changes in occupation were most common for patients without special education.

Do positive nickel reactions increase nonspecific patch test reactivity?

The patch test reaction pattern in nickel-positive and -negative female patients was compared. Cobalt allergy was found in 24.8% of the positive patients. However, the occurrence of allergy to other common agents, i.e., neomycin, perfume mix, balsam of Peru and bacitracin, did not differ significantly between the 2 groups. Even in patients allergic to nickel and cobalt simultaneously, the frequencies were comparable. Chromate and PPDA allergy was significantly commoner in nickel sensitive patients (p less than 0.05 and p less than 0.01). Erythematous or follicular reactions were seen most often to wood tars, propylene glycol, formaldehyde, cobalt, chromate and perfume mix. Reactions to propylene glycol and perfume mix were as frequent in both groups, whereas formaldehyde, cobalt and chromate caused reactions more often in nickel-positive patients (p less than 0.05) and wood tars in negatives (p less than 0.05). Follicular reactions developed especially in patients who were positive to nickel and cobalt. The total number of non-specific reactions was not overpresented in nickel sensitive patients, despite their multiple patch test reactivity.

The renin-aldosterone system in low-dose chlorothiazide treatment of hypertensive subjects.

Eight patients with essential hypertension were treated with chlorothizide 250 mg daily for 4 weeks with 500 mg daily for further 8 weeks. Both systolic and diastolic blood pressures (BP) decreased significantly during the lower dosage (p < 0.05). Only the diastolic BP continued decrease during the higher dosage regimen of chlorothiazide (p < 0.05). Plasma renin activity (PRA) and plasma aldosterone (PA) did not increase during the lower dosage of chlorothiazide. During 4 weeks on the dosage of 500 mg of chlorothiazide daily, PRA increased by 79 per cent (p < 0.001) and PA by 66 per cent (p < 0.001) from the level of the lower dosage. During the next 4 weeks, no changes in PRA or PA were seen. The result shows the strong compensatory activation renin-aldosterone system on the usual chlorothiazide therapy. In spite of a decrease in BP, the lower dosage was not accompanied with any significant compensation. Renin-aldosterone system during diuretic therapy not only causes the so-called false tolerance to antihypertensive effect, but also potentiates the loss of potassium. This can best be avoided by using the minimal effective dosage of the diuretic drug.

24 and 48 h allergen exposure in patch testing. Comparative study with 11 common contact allergens and NiCl2.

Patch test reactions to 11 common contact allergens were studied after 24 h and 48 h occlusion with Finn Chambers in 390 patients. Concordant allergic results were found in 96 cases (74%). In 22 patients (17%), the reaction was positive only after 48 h and in 11 cases (8.5%) only after 24 h exposure. Most of the discordant reactions were to nickel, cobalt, neomycin, formaldehyde and perfume mix. Irritant reactions were found in 55 cases, the majority occurring after 48 h occlusion. Nickel chloride tested in parallel with 48 h exposure lead to more positive allergic and toxic reactions than nickel sulphate.

Atopy and hand dermatitis in hospital wet work.

The relation of different atopic symptoms to the occurrence of hand dermatitis in employees who perform wet work in hospitals was studied. Atopy was defined as previous or present atopic dermatitis (AD), allergic rhinitis/conjunctivitis or asthma (AMS). In this population the prevalence of atopy was 32% and the frequency of past or present hand dermatitis 44%. Hand dermatitis had occurred in about 65% of persons with atopic symptoms and in 75% of those who had unusually dry, pruritic skin and of those with atopic relatives. Of the other workers only 33% had had skin problems. The presence of atopic symptoms significantly favoured the development of hand dermatitis in these occupations (p less than 0.001).

Nickel sensitivity and the course of atopic dermatitis in adulthood.

The course of dermatitis was followed in nickel-sensitive and nickel-negative atopic and non-atopic patients. Manifest dermatitis was seen in 70% of the nickel-allergic and in 64% of the nickel-negative female atopic dermatitis (AD) patients. Those atopic subjects who had minor symptoms in their teens suffered more from dermatitis if they had developed nickel allergy (p less than 0.025). Hands and the head region were the most common sites for current dermatitis in both groups.

Sensitivity to rubber. Study with rubber mixes and individual rubber chemicals.

During a 3-year period 3332 patients were patch tested with ICDRG standard series including 4 rubber mixes. Additional tests were performed with individual rubber chemicals and suspected solid rubber products. Rubber sensitivity was detected in 158 (4.7%) patients. Thiuram mix caused most of the positive reactions (73) followed by carba mix (51), PPD mix (40) and mercapto mix (19). From the individual rubber chemicals TMTM, TETD and IPPD caused allergic reactions most frequently. Rubber mixes, especially thiuram and PPD mix appeared to be better screening agents than any individual chemical to detect rubber allergy. However, MBT is recommended to be tested separately. Carba mix caused several irritant reactions. Three immediate type rubber reactions were seen. Gloves were the most common individual sources of rubber sensitivity.

Cutaneous adverse reactions to clindamycin: results of skin tests and oral exposure.

BACKGROUND: Clindamycin is an antibiotic used in anaerobic and severe complicated infections. It is often selected for patients with a history of allergy to other antibiotics. OBJECTIVES: To study the occurrence of clindamycin hypersensitivity and to determine whether skin tests are useful in cases of suspected clindamycin allergy. METHODS: Six patients with an exanthematous rash and a history strongly suggestive of clindamycin hypersensitivity were studied with skin tests and oral exposure. Cases of suspected adverse drug reactions to clindamycin reported to the National Register of Adverse Effects of Drugs (NRAED) in Finland during 1973-2000 were analysed. RESULTS: In the skin tests true-positive patch test reactions were seen in four of six patients, while 22 healthy control patients were negative. One false-positive and one false-negative patch test reaction were seen. During 1973-2000, 29 suspected cases of skin and/or mucosal membranes affected by clindamycin were reported to the NRAED. CONCLUSIONS: Clindamycin hypersensitivity is not common. Delayed-type allergic reactions occur and patch tests are useful in those cases. Oral exposure is the method of choice if possible, as false-negative and false-positive reactions may occur.

Dermatologic considerations in worker fitness evaluation.

Dermatoses account for a very high percentage of all occupational diseases. The authors review individual factors that increase the risk of work-related skin disease and present information to assist in the evaluation of individuals in preemployment situations and for guidance and counseling prior to occupational choices.